Bevacizumab (Avastin®) is a humanized monoclonal antibody that produces angiogenesis inhibition by inhibiting vascular endothelial growth factor A (VEGF-A).VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. 

Bevacizumab-awwb (Mvasi®), bevacizumab-bvzr (Zirabev®), bevacizumab-maly (Alymsys®), bevacizumab-adcd (Vegzelma®) and bevacizumab-tnjn (Avzivi ®) are biosimilars of bevacizumab (Avastin).

Preferred Products

Bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev) are the preferred bevacizumab biosimilars for individuals initiating new therapy for oncologic indications when the clinical criteria within this policy are met.

A non-preferred product, bevacizumab (Avastin), bevacizumab-maly (Alymsys), bevacizumab-adcd (Vegzelma) or bevacizumab-tnjn (Avzivi), will be considered when the individual has a documented therapy failure after an adequate therapeutic trial of a preferred product, or the preferred product has not been tolerated or is contraindicated.

Adequate therapeutic trial is defined as 180 days from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

New therapy is defined as no previous utilization within the last 180 days calendar days.

Bevacizumab (Avastin) or a bevaizumab biosimilar (Mvasi, Zirabev, Alymsys, Vegzelma, Avzivi) may be considered medically necessary for individuals 18 years of age and older who meet ANY ONE of the following criteria:

Cervical Cancer

• For the treatment of persistent, recurrent or metastatic cervical cancer in combination with ONE of the following:
  • Paclitaxel and cisplatin; or
  • Paclitaxel and topotecan; or

Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• For treatment in ANY of the following:
  • In combination with carboplatin and paclitaxel, followed by bevacizumab (Avastin) as a single agent, for stage III or IV disease following initial surgical resection; or
  • In combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for individuals with platinum-resistant recurrent disease who received no more than two (2) prior chemotherapy regimens; or
  • In combination with ANY of the following regimens, followed by bevacizumab (Avastin) as a single agent for platinum-sensitive recurrent disease:
    • In combination with carboplatin and paclitaxel; or
    • In combination with carboplatin and gemcitabine; or

Glioblastoma

• For treatment of recurrent glioblastoma; or

Hepatocellular Carcinoma

• For the treatment of individuals with unresectable or metastatic hepatocellular carcinoma in combination with atezolizumab who have not received prior systemic therapy; or

Metastatic Colorectal Cancer

• In combination with intravenous 5-fluorouracil-based chemotherapy for first or second-line treatment; or
• As second-line treatment in individuals who have progressed on a first-line bevacizumab (Avastin)-containing regimen in ONE of the following:
  • In combination with fluoropyrimidine-irinotecan; or
  • In combination with fluoropyrimidine-oxaliplatin; or

Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

• In combination with carboplatin and paclitaxel as first-line treatment of individuals with unresectable, locally advanced, recurrent or metastatic non-squamous cell type NSCLC; or

Renal Cell Carcinoma

• For treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Compendia Sources

Bevacizumab (Avastin) and bevacizumab biosimilars (Mvasi, Zirabev, Alymsys, Avzivi) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of bevacizumab (Avastin) and bevacizumab biosimilars (Mvasi, Zirabev, Alymsys, Vegzelma, Avzivi)  for any other oncologic indication is considered not medically necessary.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

*Note: Bevacizumab (Avastin)-containing regimens should be used with caution and withheld for at least 6 weeks prior to interval debulking surgery due to potential interference with postoperative healing.

Limitation of Use: Bevacizumab-awwb (Mvasi), bevacizumab-bvzr (Zirabev), bevacizumab-maly (Alymsys), bevacizumab-adcd (Vegzelma) and bevacizumab-tnjn (Avzivi) are not indicated for adjuvant treatment of colon cancer.

Note: Biologic therapy is only appropriate for continuation of favorable response from conversion therapy.

If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.